[unreadable] P2D, Inc. is developing a synthetic melatonin analog, PD6735, for the treatment of anxiety. Preliminary Studies suggest that PD6735 reduces anxiety in rodents. Additional pre-clinical studies indicate that PD6735 is safe and is a high-affinity melatonin agonist at MT1 and MT2 receptors. The goal of this Phase 1 SBIR proposal is to determine PD6735 efficacy in pre-clinical rodent models of anxiety. Preliminary Studies indicate that PD6735 significantly affects open field behaviors associated with anxiety: freezing (immobility) and rearing. Immobility and rearing are thought to be anxiety-related measures which are responsive to clinically effective anti-anxiety drugs (anxiolytics). We propose to extend our Preliminary Studies and perform more detailed PD6735 dose-response and time-course studies employing the open field test as well as two other anxiolytic screening tests: 1) the elevated plus maze, and 2) defensive prod-burying. Immediately after behavioral testing PD6735 plasma and brain levels will be assayed to determine the relationship between PD6735 levels and PD6735's anxiolytic effects. As PD6735 is already in clinical development, it can be evaluated relatively rapidly as an anxiolytic in humans should pre-clinical efficacy studies be positive. The Specific Aims of our Phase 1 study are: Specific Aim 1: Determine the time course of the anti-anxiety effect of acute PD6735 in the rodent open field test employing melatonin and diazepam as controls. Specific Aim 2: Measure plasma and brain PD6735 levels in Specific Aim 1 animals immediately after behavioral testing and determine the relationship between anxiety measures and plasma/brain PD6735 levels. Specific Aim 3: Determine the time course of the anti-anxiety effect of acute PD6735 in the rodent elevated plus maze model of anxiety employing melatonin and diazepam as controls. Further, measure plasma and brain PD6735 levels immediately after behavioral testing and determine the relationship between anxiety measures and plasma/brain PD6735 levels. Specific Aim 4: Determine the time course of the anti-anxiety effect of acute PD6735 in the rodent defensive prod-burying model of anxiety employing melatonin and diazepam as controls. Further, measure plasma and brain PD6735 levels immediately after behavioral testing and determine the relationship between anxiety measures and plasma/brain PD6735 levels. [unreadable] [unreadable] [unreadable]